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Glycosylated RGD-Containing Peptides: Tracer for Tumor Targeting and Angiogenesis Imaging with Improved Biokinetics

Department of Nuclear Medicine and Institute of Organic Chemistry and Biochemistry, Technische Universität München, Munich; and Department of Preclinical Oncology, Merck KGaA, Darmstadt, Germany

View larger version (17K): [in a new window]   FIGURE 1. Schematic structure of first generation tracer [125I]P2 and new glycosylated tracer [125I]GP2. Both peptides show characteristic ßII'-turn with D-Tyr in i + 1 position and RGD site in -turn conformation responsible for Vß3 selectivity.

View larger version (30K): [in a new window]   FIGURE 2. Comparison of biodistribution data of [125I]P2 () and [125I]GP2 () in melanoma-bearing nude mice and in BALB/c mice with osteosarcoma. Error bars denote SD. For some data points, error bars are not visible, because SD was smaller than size of symbol. p.i. = postinjection.

View larger version (14K): [in a new window]   FIGURE 3. Activity accumulation in tumor after pretreatment using Vß3-selective peptide cyclo(-Arg-Gly-Asp-D-Phe-Val-) in melanoma-bearing nude mice (n = 3). Data were determined 60 min after injection of [125I]P2 or [125I]GP2. Cyclo(-Arg-Gly-Asp-D-Phe-Val-) was injected 10 min before tracer injection. Right columns show activity accumulation 60 min after injection of tracer as control.

View larger version (62K): [in a new window]   FIGURE 4. Gamma-camera image 240 min after intravenous injection of 555 kBq [125I]GP2 of osteosarcoma-bearing BALB/c mouse. Contrasting tumor is clearly shown on left flank. Only additional higher activity concentration was found in intestine and in thyroid.